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Macromolecules 2008, 41, 4120-4126
Reversible Addition Fragmentation Chain Transfer (RAFT) and Hetero-Diels-Alder Chemistry as a Convenient Conjugation Tool for Access to Complex Macromolecular Designs Andrew J. Inglis, Sebastian Sinnwell, Thomas P. Davis, Christopher Barner-Kowollik,* and Martina H. Stenzel* Centre for AdVanced Macromolecular Design (CAMD), School of Chemical Sciences and Engineering, The UniVersity of New South Wales, Sydney, NSW 2052, Australia ReceiVed January 31, 2008; ReVised Manuscript ReceiVed April 7, 2008
ABSTRACT: The combination of RAFT chemistry and the hetero-Diels-Alder (HDA) cycloaddition was successfully utilized in the synthesis of poly(styrene) (PS) star polymers with up to 4 arms. This variant of the “coupling onto” method of star polymer synthesis was investigated for two different RAFT end groups (diethoxyphosphoryldithioformate and pyridin-2-yldithioformate) and coupling agents bearing 2, 3, or 4 diene functional groups. When a diethoxyphosphoryldithioformate terminated polymer was reacted with the 2-, 3-, and 4-fold functionalized coupling agents, the yields of 2-arm star, 3-arm star, and 4-arm star polymers were 81%, 77%, and 65%, respectively, and when a pyridin-2-yldithioformate terminated polymer was reacted with the same coupling agents, the yields of 2-arm star, 3-arm star and 4-arm star polymers were 91%, 86% and 82% respectively. The HDA coupling reaction was monitored via UV/vis spectroscopy from the perspective of the RAFT end group as well as by 1H NMR spectroscopy from the perspective of the diene functionality. The results of these investigations indicated that the phosphoryldiethoxydithioformate terminated polymer achieves 92% conversion within a 24 h time frame and the pyridin-2-yldithioformate terminated polymer achieves 96% conversion in 10 h. The 4-arm star polymers were also subjected to high-temperature environments, and GPC measurements indicated that complete cleavage of all 4 arms from the core was achieved in 24 h at 160 °C.
Introduction The relationship between the form and function of polymeric materials is the fuel that drives the development of the set of tools with which organic chemists can construct macromolecules of predetermined architecture. Some of the more notable inclusions in this “toolbox” are the various forms of living/ controlled free radical polymerization (CRP), which aim to combine the convenience of free radical chemistry with the control over molecular architecture that is offered by such techniques as living anionic polymerization.1,2 More recently, the combination of these techniques with “click” chemistry has significantly diversified the contents of this “toolbox”, which has allowed macromolecules with complex architecture to be synthesized with great ease.3–6 An example of such structures is star polymers. Star polymers have been the subject of intense investigation in the field of material science due to their compact structure, unusual solution properties, and unique rheological behavior.7,8 Initially, living anionic polymerization has been the method of choice in the synthesis of such structures; however, very stringent reaction conditions and the limited range of monomers that may be used means that anionic polymerization is not as versatile nor as convenient as free radical techniques. More recently, the development of the CRP technologies has brought with it resurgence in interest in the synthesis of these architectures.2,9,10 Within the field of CRP, polymeric star architectures may be synthesized utilizing one of two general techniques: corefirst10–15 and arm-first.16–19 The former technique involves the use of a multifunctional initiator whereby the arms of the star are grown from the core during the polymerization. With techniques such as reversible addition fragmentation chain * Corresponding authors. E-mail:
[email protected];
[email protected].
transfer (RAFT), atom transfer radical polymerization (ATRP), and nitroxide mediated polymerization (NMP) having been successfully shown to produce well-defined stars by the corefirst method, the RAFT process has been shown to be more cumbersome in attaining such structures.17 The arm-first technique, as it is applied to CRP, initially involved the chain extension of linear polymers with a multivinyl cross-linker. Another approach to the arm-first technique involves the “grafting” or “coupling” of linear polymer segments onto a multifunctional core. This latter method is limited by the selectivity and efficiency of the reactions responsible for linking the linear segments to the core. It has only been recently that, with the advent of the Cu(I) catalyzed ligation of azides and alkynes,20 there has been sharp increase in the reported syntheses of well-defined star polymers via the arm-first method21–26 and in polymer chemistry in general.27–29 This “click” reaction, as defined by Sharpless et al.,30 bears the selectivity and efficiency necessary to make an arm-first strategy for star polymer synthesis viable. In addition to the above-mentioned “click” reaction, the Diels-Alder cycloaddition between anthracene derivatives and maleimides has also been successfully used in the generation of a variety of well-defined polymeric architectures, including diblock copolymers,31 triblock copolymers,32 graft polymers,33 and star polymers.34 However, both of the strategies bear characteristics that may prove to be problematic in certain applications. For example, the requirement of using toxic copper catalysts in the classical “click” reaction would also have the requirement of a purification stage in the development of materials destined for biomedical application. With regard to the Diels-Alder “click” reaction, the high temperatures required make it unsuitable for use in forming polymeric conjugates from thermally unstable compounds. Another characteristic that both techniques share is that both the core and the polymer segments need to be prefunctionalized with the appropriate complementary moieties in addition to those responsible for performing the
10.1021/ma8002328 CCC: $40.75 2008 American Chemical Society Published on Web 05/20/2008
Macromolecules, Vol. 41, No. 12, 2008 Scheme 1. Hetero-Diels-Alder Reaction of Electron-Deficient Dithioesters
controlled/living polymerization. For example, in the case of RAFT, the controlling agents must be equipped with azide/ alkyne functionalities.6,35,36 Recently, Barner-Kowollik and Stenzel reported an alternative strategy for synthesizing polymer conjugates that is uniquely used with RAFT chemistry.37 Here, controlling agents bearing electron-withdrawing Z-groups (benzyl (diethoxyphosphoryl)dithioformate and benzylpyridin-2-yldithioformate) were used in such a way that the thiocarbonyl functionality of the controlling agents was sequentially used for the CRP and as a reactive heterodienophile in a hetero-Diels-Alder (HDA) cycloaddition with an appropriate diene. It was shown that the tendency of electron-deficient dithioesters to undergo HDA cycloadditions (Scheme 1) can be successfully used for the formation of block copolymers from dissimilar monomer families. The HDA cycloadditions are facilitated by the use of a catalyst which enhances the electron-withdrawing nature of the RAFT Z-group. This can be achieved by using ZnCl2 as a Lewis acid in the case of the phosphoryl Z-group38 and by trifluoroacetic acid (TFA) as a Brønsted acid in the case of the pyridinyl Z-group.39 Although achieving the same effect, the catalysts were selected on the basis of the nature of their interaction with the RAFT Z-group: the ZnCl2 chelates with the oxygen on the phosphinyl group, whereas the H+ from the TFA protonates the nitrogen on the pyridinyl group. In order to verify the versatility of this method, we herein report the synthesis of star polymers by a combination of RAFT chemistry and the HDA cycloaddition. Poly(styrene) prepared by RAFT chemistry is coupled to a 2-arm, 3-arm, and 4-arm diene precursor to form star polymers with 2, 3, and 4 arms, respectively. The reaction used to generate these structures was then monitored via UV/vis spectroscopy and 1H NMR spectroscopy from the perspective of the RAFT end group and the diene, respectively. Finally, in order to investigate the possibilities of induced cleavage of the 4-arm stars, the compounds were subjected to a high-temperature environment for 24 h, and subsequent GPC measurements were performed. The present contribution provides a simple and synthetically nondemanding pathway to well-defined macromolecular starshaped architectures which provides a convenient exemplification for this new synthetic technique. Experimental Section Materials and Characterization. Benzyl (diethoxyphosphoryl)dithioformate (1a)40 and benzylpyridin-2-yldithioformate (1b)41 were synthesized according to the literature. Styrene (g99%, Aldrich) was passed through a column of basic alumina (Ajax Finechem) and stored at -19 °C. 2,2′-Azobis(isobutyronitrile) (AIBN, DuPont) was recrystallized twice from methanol before use and stored at 4 °C. trans,trans-2,4-Hexadien-1-ol (97%, Aldrich), 1,4-bis(bromomethyl)benzene (97%, Aldrich), 1,3,5-tris(bromomethyl)benzene (97%, Aldrich), 1,2,4,5-tetrakis(bromomethyl)benzene (95%, Aldrich), THF (g99.9%, anhydrous, water
